Abstract
Inherited germline variants in urothelial cancer: A multicenter whole-exome sequencing analysis
Journal of clinical oncology, Vol.40(6_suppl), pp.451-451
02/20/2022
DOI: 10.1200/JCO.2022.40.6_suppl.451
Abstract
451
Background: Outside of Lynch syndrome, few genetic factors have been associated with urothelial cancer (UC). This project seeks to describe the frequency of germline variants in a multi-center UC cohort. Methods: Patients diagnosed with UC from 1980 to 2019 and consented to the Total Cancer Care protocol by members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. The ORIEN program includes a convenience sample of cases with both germline and tumor samples available, though this analysis was germline only. Whole exome sequencing data were analyzed using a GATK best practices for germline variant analysis. A series of quality control (allele frequency > = 0.3, read depth > = 20, genotype quality > = 20), annotation, functional impact (loss of function/splicing), and region (cancer predisposition genes/pathways) filters were applied to identify variants of significant consequence. Results: 348 exomes were evaluated. This identified 60 variants classified as pathogenic/likely pathogenic (P/LP) and 17 novel, high impact variants in genes associated with high, moderate, or recessively inherited cancer risk in 77 individuals (22.1%). 15 (4.5%) had P/LP variants in genes associated with a high or moderate cancer risk, and 10 (3%) of these variants were considered to be clinically actionable with associated with cancer screening, risk reduction or treatment recommendations. The high/moderate risk genes with P/LP variants included CHEK2 (n = 5), FANCM (n = 4), MSH6 (n = 2) and single cases of MSH2, BRCA2, ERCC3, and BRIP1. The average age of diagnosis in those with and without a high/moderate risk P/LP variant was 67.6 (57-80 yrs) and 68.9 (45-91 yrs). Family history of cancer was reported for 73% of those with a germline LP/PV and 60% of those without, but this trend was not significant (p =.44). Conclusions: Individuals with UC have a high frequency of germline variants that warrant further study for association with cancer risk. A smaller, but significant portion also carry germline variants that may be clinically relevant to them and/or family members. Currently UC is not included in genetic testing criteria. This study adds to the growing body of research indicating that diverse types of cancer patients harbor germline variants. Strategies for expanding testing should be considered.
Details
- Title: Subtitle
- Inherited germline variants in urothelial cancer: A multicenter whole-exome sequencing analysis
- Creators
- Wendy Kohlmann - Huntsman Cancer InstituteDavid Nix - Huntsman Cancer InstituteAaron Atkinson - Huntsman Cancer InstituteKenneth M Boucher - Huntsman Cancer InstituteJill Kolesar - University of KentuckyEric A. Singer - Rutgers, The State University of New JerseyStephen B. Edge - Roswell Park Cancer InstituteBranda Quintana - Huntsman Cancer InstituteMichelle L. Churchman - M2Gen, Tampa, FL;Bingjian Feng - Huntsman Cancer InstituteLaura Graham - University of Colorado BoulderJohn D. Carpten - University of Southern CaliforniaAlejandro Sanchez - Huntsman Cancer InstituteYousef Zakharia - University of IowaLindsey Byrne - The Ohio State UniversityRohit K. Jain - Moffitt Cancer CenterKenneth G. Nepple - University of IowaAhmad Shabsigh - The Ohio State UniversityJad Chahoud - Moffitt Cancer CenterSumati Gupta - Huntsman Cancer Institute
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.40(6_suppl), pp.451-451
- DOI
- 10.1200/JCO.2022.40.6_suppl.451
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Huntsman Cancer Institute and Oncology Research Information Exchange Network.
- Language
- English
- Date published
- 02/20/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Urology
- Record Identifier
- 9984321556502771
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